ive heart failure or LVEF < 55%,uncontrolled arrhythmias, angina requiring medication, clinically significant valvular heart disease, evidence oftransmural infarction on ECG, poorly controlled hypertension (systolic > 180 mm Hg or diastolic > 100 mmHg) were not eligible.
HERA was designed to compare 1 and 2 years of three-weekly intravenous trastuzumab treatment versusobservation in patients with HER2 positive EBC following surgery, established chemotherapy and radiotherapy(if applicable). Patients were randomized (1:1:1) upon completion of definitive surgery, and at least 4 cycles of
chemotherapy to receive no additional treatment, or 1 year of intravenous trastuzumab treatment or 2 years ofintravenous trastuzumab treatment. Patients undergoing a lumpectomy had also completed standardradiotherapy. Patients with ER+ and/or PgR+ disease received systemic adjuvant hormonal therapy at
investigator discretion. Intravenous trastuzumab was administered with an initial dose of 8 mg/kg followed bysubsequent doses of 6 mg/kg once every 3 weeks. The main outcome measure was DFS, defined as inStudies NSABP B31 and NCCTG N9831.
A protocol specified interim efficacy analysis comparing one-year intravenous trastuzumab treatment toobservation was performed at a median follow-up duration of 12.6 months in the intravenous trastuzumab armand formed the basis for the definitive DFS results from this study. Among the 3386 patients randomized to the
observation (n = 1693) and intravenous trastuzumab one-year (n = 1693) treatment arms, the median age was 49years (range 21−80), 83% were Caucasian, and 13% were Asian. Disease characteristics: 94% infiltrating ductalcarcinoma, 50% ER+ and/or PgR+, 57% node positive, 32% node negative, and in 11% of patients, nodal status
was not assessable due to prior neo-adjuvant chemotherapy. Ninety-six percent (1055/1098) of patients withnode-negative disease had high-risk features: among the 1098 patients with node-negative disease, 49% (543)were ER− and PgR−, and 47% (512) were ER and/or PgR+ and had at least one of the following high-risk features: pathological tumor size > 2 cm, Grade 2−3, or age < 35 years. Prior to randomization, 94% of patientshad received anthracycline-based chemotherapy regimens.
After the definitive DFS results comparing observation to one-year intravenous trastuzumab treatment weredisclosed, a prospectively planned analysis that included comparison of one year versus two years ofintravenous trastuzumab treatment at a median follow-up duration of 8 years was performed. Based on this
analysis, extending intravenous trastuzumab treatment for a duration of two years did not show additionalbenefit over treatment for one year [Hazard Ratios of two-years intravenous trastuzumab versus one-yearintravenous trastuzumab treatment in the ITT population for DFS = 0.99 (95% CI: 0.87, 1.13), p = 0.90 and
OS = 0.98 (0.83, 1.15); p = 0.78].
BCIRG006 Study
In the BCIRG006 Study, breast tumor specimens were required to show HER2 gene amplification (FISH+ only)as determined at a central laboratory. Patients were required to have either node-positive disease, ornode-negative disease with at least one of the following high-risk features: ER/PR-negative, tumor size > 2 cm,age < 35 years, or histologic and/or nuclear Grade 2 or 3. Patients with a history of CHF, myocardial infarction,Grade 3 or 4 cardiac arrhythmia, angina requiring |
